sequelas fonoaudiológicas após tratamento para câncer de...
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ISABELA PORTO DE TOLEDO
Sequelas Fonoaudiológicas após tratamento para câncer de cabeça e
pescoço
BRASÍLIA, 2018
2
UNIVERSIDADE DE BRASÍLIA
FACULDADE DE CIÊNCIAS DA SAÚDE
PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE
ISABELA PORTO DE TOLEDO
Sequelas Fonoaudiológicas após tratamento para câncer de cabeça e
pescoço
Dissertação apresentada como requisito
parcial para a obtenção do título de
Mestre em Ciências da Saúde pelo
programa de Pós-Graduação em
Ciências da Saúde da Universidade de
Brasília.
Orientadora: Profa. Dra. Eliete Neves da
Silva Guerra
Coorientadora: Profa. Dra. Graziela De
Luca Canto
BRASÍLIA, 2018
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ISABELA PORTO DE TOLEDO
Sequelas Fonoaudiológicas após tratamento para câncer de cabeça e
pescoço
Dissertação apresentada como requisito
parcial para a obtenção do título de
Mestre em Ciências da Saúde pelo
programa de Pós-Graduação em
Ciências da Saúde da Universidade de
Brasília.
Aprovado em 22 de fevereiro de 2018.
BANCA EXAMINADORA
Profa. Eliete Neves da Silva Guerra – presidente
Universidade de Brasília
Profa. Paula Elaine Diniz dos Reis
Universidade de Brasília
Prof. Paulo Tadeu de Souza Figueiredo
Universidade de Brasília
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AGRADECIMENTOS
Agradeço aos meus pais e meu irmão pelo amor, incentivo, paciência,
conselhos e apoio incondicional.
Agradeço à minha orientadora, Profa Eliete Neves Silva Guerra, agradeço
pelas oportunidades, orientações, carinho e incentivo constante.
Agradeço à minha coorientadora, Profa Graziela De Luca Canto, pelos
ensinamentos, incentivos, pela amizade e por auxiliar no meu caminho no mundo da
pesquisa.
Às colegas Letícia L. Q. Pantoja, Karen Luchesi e Daniela Assad,
componentes da equipe da revisão sistemática, agradeço a dedicação,
disponibilidade e compartilhamento de conhecimentos.
Agradeço a equipe do COBE da Universidade Federal de Santa Catarina, por
sempre estarem disponíveis para ajudar, tirar dúvidas, dar opiniões, ideias e
conselhos.
Agradeço às colegas fonoaudiólogas, Cristina Furia e Denise Lica, agradeço
pela oportunidade de trabalhar na área oncológica, por compartilhar os valiosos
conhecimentos da prática clínica e pela amizade.
Agradeço aos meus pacientes do UNACON e enfermaria oncológica, por me
acolherem e pelas lições de vida.
Aos meus colegas do Laboratório de Histopatologia bucal, agradeço pela
amizade, auxílio com trâmites da universidade, FAP-DF e informática.
Agradeço por fim à CNPQ pela bolsa concedida que possibilitou a minha
dedicação exclusiva ao Mestrado, e a FAP-DF pela oportunidade de apresentar o
trabalho num congresso internacional.
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RESUMO
As desordens de deglutição são sequelas comumente associadas ao
tratamento oncológico. Contudo, ainda não existe um consenso quanto a frequência
de alterações do processo de deglutição nessa população. O estudo tem por
objetivo estimar a frequência de desordens da deglutição no pré e pós-tratamento
de pacientes com câncer de cabeça e pescoço. Uma revisão sistemática foi
desenvolvida seguindo o guia para relato de itens de revisão sistemática e meta-
análises (PRISMA). Estratégias de busca foram desenvolvidas para as seguintes
bases de dados: PubMed, LILACS, Scopus, Web of Science, LIVIVO e SpeechBITE.
Adicionalmente, uma busca da literatura cinzenta foi realizada através do Google
Scholar, Open Grey e ProQuest. Somente estudos que realizaram avalição
diagnóstica da deglutição utilizando exames objetivos como videofluroscopia da
deglutição ou videoendoscopia da deglutição foram incluídos na análise. O risco de
viés dos estudos incluídos foi analisado com a ferramenta “The Critical Appraisal
Checklist for Studies Reporting Prevalence Data from the Joanna Briggs Institute”. A
meta-análise de proporção, com efeito fixo ou randômico, foi realizada através do
Software estatístico MedCalc versão 14.8.1 (MedCalc Software, Ostend, Belgium). A
seleção dos estudos foi realizada em duas fases, por dois revisores,
independentemente. Dezesseis estudos passaram pelos critérios de elegibilidade e
foram incluídos para análise. Em todos os estudos a deglutição foi avaliada antes e
até 12 meses após o tratamento oncológico. Aspiração prévia a tratamento de
câncer teve frequência de 11,3% (desvio padrão (SD), 8,7 a 14,3%; amostra
total=517), entre 1 a 6 meses após tratamento ocorreu um aumento para 27,1%
(SD, 1,0 a 36,0%; amostra total=478) e até 12 meses pós-tratamento teve uma
queda para 17,9% (SD, 12,3 a 2,8%; amostra total=153). Penetração de volume
acima das pregas vocais e redução de elevação laríngea também foram mais
frequentes no período de 1 a 6 meses após tratamento oncológico. Os resultados
encontrados nesse estudo indicam que a frequência de desordens de deglutição e
suas complicações como a aspiração, em pacientes com câncer de cabeça e
pescoço aparenta ser maior no período de até 6 meses após tratamento para o
câncer.
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ABSTRACT
The deglutition disorders are common sequelae of the oncologic treatment.
However, there is no consensus over the frequency of the alteration in the
swallowing mechanisms in this population. The study aims to estimate the frequency
of deglutition disorders in patients pre and post-treatment for head and neck cancer.
A systematic review was developed following the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) guideline. Search strategies
were developed for the following databases: PubMed, LILACS, Scopus, Web of
Science, LIVIVO, and SpeechBITE. Additionally, a search of the grey literature was
performed through Google Scholar, Open Grey, and ProQuest. Only studies that
performed evaluation of deglutition before and after cancer treatment were included
in this systematic review. The studies had to use diagnostic exams for deglutition
disorders as Videofluoroscopy swallowing exam, Fiber-optic endoscopic evaluation
of swallowing, modified barium swallow or Videofluorographic swallow study. The
Critical Appraisal Checklist for Studies Reporting Prevalence Data from the Joanna
Briggs Institute was used to assess the risk of bias of the included studies. A
proportion of fixed or random effects meta-analysis using the MedCalc Statistical
Software version 14.8.1 (MedCalc Software, Ostend, Belgium) were conducted. The
selection of the studies was divided in two phases where two reviewers worked
independently. Sixteen studies met the eligibility criteria and were included. In all of
the studies an assessment of the deglutition was performed previous and up to 12
months after receiving treatment for the cancer. Aspiration previous to the cancer
treatment had a frequency of 11.3% (Standard deviation (SD), 8.7 to 14.3%; total
sample=517), between 1 to 6 months after treatment, this increased to 27.1% (SD,
19.0 to 36.0%; total sample=478), and up to 12 months after there was a decrease
to 17.9% (SD, 12.3 to 24.8%; total sample=153). Penetration above the vocal cords
and reduced larynx elevation were also more frequent in the 1 to 6 months’ period
after the treatment for the head and neck cancer. The results found in this study
indicates that the frequency of deglutition disorders and its complications as
aspiration, in patients with head and neck cancer, appears to be higher in the
immediate to 6 months’ post-treatment period.
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LISTA DE FIGURAS
Figuras da Dissertação:
- Figura 1: Fases da deglutição normal, adaptado de Logemann e Logemann,
1983.
- Figura 3: Descrição adaptada dos passos de uma revisão sistemática.
Figuras do Artigo científico:
- Figure 1. Flow Diagram of Literature Search and Selection Criteria.
- Figure 2a. Meta-analysis graphs and data for aspiration in three different
periods.
- Figure 2b. Meta-analysis graphs and data for penetration in three different
periods.
- Figure 2c. Meta-analysis graphs and data for reduced laryngeal elevation in
two different periods.
- Figure 2d. Meta-analysis graphs and data for aspiration different cancer
treatment modalities.
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LISTA DE TABELAS
Tabelas do artigo científico
• Table 1: Summary of study descriptive characteristics of included studies
(n=16).
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LISTA DE ABREVIATURAS E SIGLAS
AJCC = American Joint Committee on Cancer
CCP = Câncer de Cabeça e Pescoço
DARS = Dysphagia/aspiration-related structures
EUA = Estados Unidos da América
IMRT = Radioterapia de intensidade modulada
MA = Meta-análise
RAD = Late radiation-associated dysphagia
RS = Revisão Sistemática
SWAL-QOL= Swallowing quality of life questionnaire
WHO = Oral Mucositis Grading Scale
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SUMÁRIO
1 INTRODUÇÃO.................................................................. 11
2 REVISÃO DA LITERATURA ........................................... 12
2.1 CÂNCER DE CABEÇA E PESCOÇO........................ 12
2.2 SEQUELAS BUCAIS ................................................. 13
2.3 DESORDENS DA DEGLUTIÇÃO............................... 14
2.4 REVISÃO SISTEMÁTICA .......................................... 16
3 PROBLEMA DE PESQUISA ........................................ 18
3.1 HIPÓTESES............................................................... 18
4 OBJETIVOS..................................................................... 18
4.1 OBJETIVO GERAL .................................................... 18
4.2 OBJETIVOS ESPECÍFICOS ..................................... 18
5 ARTIGO CIENTÍFICO ..................................................... 19
6 CONSIDERAÇÕES GERAIS .......................................... 76
7 CONCLUSÕES................................................................ 78
REFERÊNCIAS BIBLIOGRÁFICAS ............................... 79
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1. INTRODUÇÃO
A conduta terapêutica nos quadros oncológicos de cabeça e pescoço requer
ação multiprofissional, incluindo profissionais como: cirurgião de cabeça e pescoço,
oncologista, radiologista, fonoaudiólogo, cirurgião-dentista, nutricionista, assistente
social, psicólogo, fisioterapeuta, enfermeiro, entre outros. A atuação do
fonoaudiólogo é voltada, principalmente, para as funções relacionadas à
alimentação e à comunicação. Essa atuação, quando possível, deve ocorrer desde
o período de diagnóstico do câncer1.
As desordens de deglutição são exemplos de alterações comumente
associadas às neoplasias em cabeça e pescoço. A avaliação da deglutição e
demais funções do sistema estomatognático é realizada pelo fonoaudiólogo em
ambiente clínico. Se necessário, a avaliação complementar pode ser realizada com
exames objetivos, como a videofluoroscopia2.
Na reabilitação da função de deglutição, o fonoaudiólogo pode empregar
diferentes estratégias, como modificação de consistência alimentar, estratégias
posturais, manobras de proteção das vias aéreas e ainda, exercícios terapêuticos
para os grupos musculares envolvidos no processo de deglutição3. Contudo, não há
na literatura um consenso quanto à utilização dessas estratégias para terapia
profilática nos pacientes oncológicos.
Essa lacuna no meio científico pode levar à falta de consenso sobre dados de
frequência das desordens de deglutição antes e após o tratamento oncológico. Um
maior conhecimento sobre essa frequência previamente à terapia oncológica e após
a sua conclusão são fundamentais para o entendimento dessas alterações e para
as possibilidades de intervenção.
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2. REVISÃO DE LITERATURA
2.1 Câncer de cabeça de Pescoço
O Carcinoma de Cabeça e Pescoço (CCP) pode surgir na região de lábios,
cavidade oral, orofaringe, hipofaringe, nasofaringe, laringe, glândulas salivares,
cavidade nasal e seios paranasais, meato acústico externo e ouvido médio4. O CCP
tem como característica uma incidência maior em homens do que em mulheres,
comumente encontrados na população de baixo nível socioeconômico, com
diagnostico após a meia-idade. Fatores de risco relacionados com o surgimento
desses tipos de carcinomas incluem o tabaco, álcool e infecções de papilomavírus
humano (HPV), especialmente do subtipo 165.
A prevalência dos casos de tumores em cavidade oral e lábios no mundo é
de 2,2%, seguida de 1,4% em laringe, 1,0% em faringe e 0,7% em nasofaringe6.
Nos EUA estima-se que mais de 50 mil novos casos de câncer de cavidade oral e
faringe irão ocorrer em 2018, sendo 37.160 desses casos em homens7. No Brasil,
estima-se que para o biênio de 2018-2019, mais de 11.200 mil casos de câncer de
cavidade oral acometerão a população masculina, mais do que o dobro do valor
comparado a população feminina (3.500)8.
O diagnóstico de CCP possui como guia a classificação criada pelo American
Joint Committee on Cancer (AJCC), que classifica o câncer em diferentes estágios,
de inicial (estágios I e II) a avançado (estágios III e IV)9. Conhecer a extensão e/ou
estágio de câncer quando este é diagnosticado é um fator importante para a
formação de decisão quanto ao tratamento e prognóstico. A média de tempo para
diagnóstico de CCP é de 17 semanas10.
O principal objetivo quando se planeja a proposta terapêutica para tumores
malignos é a cura. Contudo, objetivos secundários também são importantes para
manejo das possíveis sequelas pós-tratamento. Um dos objetivos secundários do
tratamento de CCP é a preservação de funções11. As modalidades convencionais e
aplicadas na prática clínica para CCP são: cirurgia como primeira opção de
tratamento curativo, radioterapia e quimioterapia quando indicado. Dependendo do
estágio em que o câncer foi diagnosticado (estágios avançados), pode-se realizar
uma combinação de duas ou das três modalidades11.
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Dentre as diferentes técnicas para execução de radioterapia, a de
intensidade modulada (IMRT), auxilia na preservação de estruturas essenciais para
realização de funções. Essa modalidade terapêutica possui tecnologia de
conformação de radiação, o que auxilia na distribuição da dose de radiação, como
na diminuição da exposição de estruturas e tecidos circunjacentes ao tumor, porém
não afetados pela doença12. IMRT associada a técnica de imagem guiada, também
auxilia na distribuição da dose da radiação, permitindo reprogramações em tempo
real da posição, volume e da dose a ser aplicada13.
2.2 Sequelas Bucais
Sequelas durante e pós-tratamento para CCP são esperadas e muitas vezes
prejudiciais às funções do sistema estomatognático, como mastigação, deglutição e
fala. Durante e/ou após a radioterapia, quimioterapia ou combinação dessas, é
comum aparecerem alterações como mucosite, dor em região oral, disfagia, perda
de peso, alterações no paladar, xerostomia, diminuição da abertura de boca e
osteorradionecrose14.
A mucosite oral é uma inflamação da mucosa oral e/ou orofaríngea,
geralmente com surgimento durante a radioterapia e/ou quimioterapia. Essa
inflamação causa dor, desconforto na região oral e interfere na ingestão de
alimentos, deglutição, e higiene oral15. A severidade da mucosite oral pode ser
classificada por meio da escala Oral mucositis grading scale (WHO), onde zero é o
equivalente a sem alteração da mucosa e 4 é a mucosite severa com
impossibilidade de alimentação por via oral. O surgimento dessa inflamação em
mucosa é comum nas semanas iniciais do tratamento de radioterapia (2-3
semana)16. A prevalência de mucosite em pacientes com CCP, durante tratamento
combinado de IMRT e cisplatina foi de 54% (n=39). Após três meses do término do
tratamento, ocorreu uma queda para 23% (n=39)17.
Outra sequela comumente presente durante e após terapêutica de CCP é a
xerostomia. Esse sintoma é caracterizado pela sensação de boca seca e/ou saliva
espessa18. A hipossalivação é uma alteração que ocorre nas glândulas salivares,
podendo ser causada pela radioterapia/quimioterapia, e possui como característica
a baixa produção de saliva, acarretando em sensação de boca seca19. A ocorrência
de xerostomia em pacientes com CCP após três e seis meses do final do tratamento
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foi de 43% e 36%, respectivamente20. Um dos fatores que podem contribuir com a
diminuição dessa sequela, é o planejamento radioterapêutico. Numa amostra de
pacientes com câncer em orofaringe submetida a radioterapia poupando as
glândulas submandibulares contralaterais, foi observado diminuição de xerostomia
quando comparado ao grupo onde as glândulas não foram poupadas21. Contudo,
outros fatores podem estar associados com o surgimento da xerostomia, como o
uso de opioides, consumo de álcool, cigarro, idade, entre outros.
O trismo consiste da redução da abertura da boca (<35 mm), geralmente
associada a radiação em cabeça e pescoço, causando mudanças na contratura das
estruturas da mastigação18. Essa alteração na abertura de boca gera
consequências para as funções de mastigação e fala. Dez anos após tratamento de
radioterapia, numa amostra com CCP, foi observado que 55% (n=22) dos pacientes
apresentavam trismo21. A dose de radioterapia também foi associada a
probabilidade de desenvolver trismo, onde observou-se que a cada 10 Gy adicionais
no músculo pterigoideo, depois de uma dose de 40 Gy, houve aumento de 24%
(n=56) na probabilidade de desenvolver trismo22.
2.3 Desordens de deglutição
As desordens no processo de deglutição ou disfagia, é uma das alterações
que pode ser encontrada em pacientes com CCP no decorrer da doença, durante e
após o tratamento. Na deglutição normal, o alimento passa da cavidade oral para a
faringe e em seguida ao esôfago em questão de poucos segundos (~2 segundos)
(Figura 1)23. Qualquer alteração nesse processo ou em suas estruturas podem levar
a disfagia.
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Figura 1 – Fases da deglutição normal, adaptado de Logemann e Logemann
(1983)23.
As disfagias associadas ao CCP são geralmente alterações mecânicas na
região oral e/ou faríngea. A disfagia orofaríngea é uma alteração do processo de
transferência do bolo alimentar ou líquido da cavidade oral para o esôfago. Nesse
processo de transferência, as complicações podem ocorrer, como penetração de
volume alimentar acima das pregas vocais e até a aspiração deste em vias aéreas.
Outro tipo de disfagia é a esofágica, onde há uma alteração na passagem do
alimento do esôfago até o estômago24.
Um dos tipos de disfagia decorrentes da radioterapia na região de cabeça e
pescoço é a Late radiation-associated dysphagia (RAD), que é resultante da fibrose
de tecidos, estenose, neuropatia craniana inferior e rigidez25. Outras alterações
associadas às terapias de câncer também podem contribuir para o surgimento ou
piora da disfagia como, mucosite, xerostomia, disgeusia, trismo e odinofagia.
A dificuldade em deglutir foi relatada como moderada em 16,9% (n=39) e
severa em 18,5% (n=39) no pós-tratamento de seis a doze meses17. Num longo
período de tempo, dez anos após tratamento finalizado, 54% (n=22) dos pacientes
Fase Preparatória: Vedamento labial,
mastigação e formação de bolo alimentar.
Fase Oral: Preparação do bolo alimentar e
início do reflexo da deglutição.
Fase Faríngea: Inicia após reflexo, com o
vedamento velofaríngeo, contrações
peristálticas para movimentar o bolo
alimentar para a faringe; elevação e
oclusão de laringe e relaxamento
cricofaríngeo para passagem de bolo
para esôfago.
Fase Esofágica: Movimentos
peristálticos para passagem do bolo
alimentar.
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com CCP apresentaram alguma limitação na alimentação21. A disfagia também
pode levar ou prolongar a alimentação por vias alternativas, que servem de aporte
nutricional. Em um estudo com 243 pacientes pós-tratamento combinado
(quimioterapia e radioterapia) para CCP, foi observado que mais de 60% da amostra
necessitou de uso de via alternativa para alimentação26.
Uma das formas de auxiliar no planejamento da radioterapia, com o intuito de
preservar as estruturas responsáveis pela deglutição é identifica-las e evita-las
durante o tratamento. As estruturas relacionadas à disfagia/aspiração (DARS) são:
palato mole e duro, músculos intrínsecos da língua, complexo muscular
milo/geniohioideo, músculo genioglosso, músculo palatoglosso, músculo bucinador,
músculo digástrico anterior e posterior, músculo pterigoideo lateral, medial, superior
e constritor, músculo constritor médio e inferior, supraglote, glote e subglote e
esfíncter cricofaríngeo25.
A disfagia e outros sintomas orais são fatores que influenciam na qualidade
de vida dos indivíduos com CCP. Numa população de pacientes com tumores
avançados em região de cabeça e pescoço foi observado piores pontuações no
questionário aplicado (SWAL-QOL), em relação aos itens alimentação e
comunicação, duração da refeição, vontade de comer e medo ou restrições em
comer em público. Esses são fatores que podem levar a um declínio da vida social,
isolamento e depressão27.
2.4 Revisão Sistemática
As técnicas de construção e desenvolvimento de pesquisa são diversas para
análise de sequelas orais associadas ao tratamento oncológico. Uma das
metodologias de pesquisa de alto nível de evidência científica são as revisões
sistemáticas (RSs). As RSs são eficientes para coletar e assimilar informações
disponíveis na literatura e utilizar esse conhecimento para a prática clínica28.
Um dos primeiros passos para a execução de uma RS é a criação de um
protocolo de pesquisa. O guia para relato de itens de revisão sistemática e meta-
análises (PRISMAp) auxilia na construção desse protocolo e na descrição dos itens
necessários de uma RS29. O protocolo deve conter uma pergunta de pesquisa
específica que contenha população alvo, intervenção ou exposição, uma
comparação (se aplicável), os resultados esperados e os tipos de estudo que
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possam responder à pergunta (PICOS). É a partir dessa pergunta que se gera todos
os outros componentes da RS.
Passos para a execução de uma RS (Figura 2)30,31:
• Desenvolvimento de pergunta de pesquisa específica (PICOS);
• Elaboração de estratégias de busca abrangentes e reproduzíveis para
diversas bases de dados;
• Construção de critérios de inclusão e exclusão bem definidos e aplicados
em todos os estudos pesquisados;
• Seleção dos estudos em 2 fases, realizadas por dois revisores,
independentemente. Fase 1 consiste em leitura de títulos e resumo, e
fase 2 da leitura do texto completo;
• Avaliação criteriosa do risco de viés dos estudos selecionados;
• Síntese qualitativa e quantitativa dos resultados encontrados;
• Inferências a partir dos resultados analisados.
A análise estatística que pode fazer parte de uma RS é a Meta-Análise (MA).
Essa análise combina e sumariza os resultados de múltiplos estudos, aumentando
assim a precisão e o poder de evidência dos resultados encontrados29.
O impacto da RS para a pesquisa e atuação clínica é um tópico amplamente
discutido. A decisão clínica é feita por meio de vários fatores: preferências e
circunstâncias do paciente; recursos disponíveis; conhecimento do profissional da
área da saúde e evidências de pesquisa válida e relevante. A prática clínica
baseada em evidência auxilia na melhora da qualidade do tratamento
disponibilizado20,32.
Figura 2 – Descrição adaptada dos passos de uma revisão sistemática30,31.
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3. PROBLEMA DE PESQUISA
A literatura apresenta dados heterogêneos sobre as desordens de
deglutição em pacientes com CCP, desde o início da doença, bem como após a
finalização do tratamento. A heterogeneidade desses dados pode ser resultante de
diversos fatores, como diferentes tipos de CCP, uso de diversas ferramentas para
acessar as desordens de deglutição, as várias modalidades terapêuticas, faixa
etária da população e estágio em que o câncer foi diagnosticado. Diante desse
panorama formulou-se a seguinte pergunta: Qual é a frequência de desordens da
deglutição pré e pós-tratamento oncológico em pacientes com CCP?
3.1 HIPÓTESES
Hipótese 1: Há uma alta frequência de desordens de deglutição nos
pacientes com câncer em região de cabeça e pescoço desde o diagnóstico da
doença.
Hipótese 2: A frequência das desordens aumenta após o tratamento
oncológico, quando comparado ao pré-tratamento.
4. OBJETIVOS
4.1 OBJETIVO GERAL
Identificar a evidência disponível na literatura científica sobre as desordens
de deglutição pré e pós-tratamento de câncer de cabeça e pescoço.
4.2 OBJETIVOS ESPECÍFICOS
• Coletar artigos científicos que apresentem dados sobre a frequência
de desordens de deglutição na população alvo;
• Analisar os dados coletados sobre as desordens de deglutição e
alterações associadas dos artigos científicos selecionados;
• Comparar resultados coletados dos estudos sobre as desordens de
deglutição e alterações associadas no pré-tratamento com no pós-
tratamento oncológico.
19
5. ARTIGO
Essa revisão sistemática, em formato de artigo, foi submetida para publicação na
revista Head & Neck, ISSN 1043-3074 (versão impressa), classificada como
periódico B1 na Qualis-Capes Medicina II. O registro do envio está sob número
HED-17-1459. A escolha da revista foi influenciada pelo escopo da revista, onde se
encontram diversas publicações na área de interesse, além de apresentar prévias
publicações de revisões sistemáticas.
Deglutition disorders as a consequence of head and neck cancer therapies: a systematic
review and meta-analysis
Running title: Frequency of deglutition disorders in HNC patients
Isabela Porto de Toledo, SLP, MSc1,4; Leticia Lopes Quirino Pantoja, DDS, MSc1; Karen
Fontes Luchesi, SLP, MSc, PhD2; Daniele Xavier Assad, MD, MSc1,5; Graziela De Luca
Canto, DDS, MSc, PhD3,4; Eliete Neves Silva Guerra*, DDS, MSc, PhD1
1Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasília, Brasília,
Brazil;
2Department of Speech Language Therapy, Federal University of Santa Catarina,
Florianopolis, SC, Brazil;
3Department of Dentistry, Federal University of Santa Catarina, Florianopolis, SC, Brazil;
4Brazilian Centre for Evidence Based Research, Department of Dentistry, Federal University
of Santa Catarina, Florianopolis, SC, Brazil;
5 Hospital Sírio-Libanês, Brasília, Brazil.
* Correspondence Author: Eliete Neves Silva Guerra; [email protected]; Telefax:
+55-61-996684988. SQN 2015, Bloco H, apto 201, Asa Norte, Brasília DF, Brazil. Zip Code:
70843-080
20
ABSTRACT
Objective: The study aims to estimate the frequency of deglutition disorders in patients pre
and post-treatment for head and neck cancer (HNC).
Methods: Search strategies were developed for the following databases: LILACS, PubMed,
SpeechBITE, LIVIVO, Web of Science and Scopus. Additionally, the grey literature was
searched through Google Scholar, Open Grey, and ProQuest. Only studies that performed
evaluation of deglutition before and after cancer treatment were included. A proportion of
fixed or random effects meta-analysis using MedCalc Statistical Software was conducted.
Results: Sixteen studies were included. Aspiration had a higher frequency between one to six
months after treatment, with 27.1% (total sample=478). Penetration of fluids above the vocal
cords and reduced laryngeal elevation were also more frequent in the same time period.
Conclusion: The frequency of deglutition disorders and its complications as aspiration
appears to be higher in the immediate to six months post-treatment in HNC patients.
Keywords: Deglutition disorders; Head and neck neoplasms; Chemoradiotherapy;
Systematic review; Meta-analysis.
21
INTRODUCTION
According to the World Health Organization Classification of Tumors (WHO), head and
neck cancers (HNC) are divided in: oral cavity, larynx, nasopharynx, oropharynx,
hypopharynx, nasal cavity and paranasal sinuses, ear, odontogenic, paraganglionic, and
salivary glands tumors1. Lip and oral cavity tumors had a prevalence of 2.1% worldwide, they
were followed by larynx cancer with 1.1%, and nasopharynx cancer with 0.6%2. In the United
States, oral cavity and pharynx cancers accounted for 34,780 new cases in the male
population in 20163. The studies over the incidence of HNC show a trend, this type of tumor
occurs more often in males over 40 years old associated to alcohol and tobacco consumption2-
4.
The treatment available for HNC may include: surgery, radiotherapy, chemotherapy or a
combination of treatments5. The course of treatment is defined based on tumor size, location,
resectability, organ preservation approach and metastatic status6. Different types of adverse
effects are expected from HNC treatments. They differ depending on treatment duration,
surgery extension, drug type and radiation location and intensity. Some examples of adverse
effects are: pain, weight loss, dry mouth, dysphagia, mucositis, dysgeusia, speech/voice
disorders, loss of appetite, changes in physical appearance, social life and in the quality of life
in general7-11.
The frequency of dysphagia in HNC differs when considering different variables such as
radiotherapy field size and radicality of surgery. Dysphagia had a higher prevalence, 63.6%
right after surgery (<1 year) compared to a longer period (>5 years)12. Similarly, dysphagia
had a prevalence of 45.9% after cancer treatments (surgery and/or radiotherapy)13.
Two previous systematic reviews (SR)14,15 investigate the changes in swallow
mechanisms after radiation or drug therapy in HNC. In neither review a quantitative analysis
was performed. Therefore, more research on the topic is necessary, because new and more
22
detailed studies have surfaced over the last 4 years16-21. There is also a need for a quantitative
analysis of the results found in the literature. Therefore, the aim of this systematic review was
to answer the following research question: “What is the frequency of deglutition disorders pre
and post treatment in patients that underwent cancer therapy for HNC?”
METHODS
This systematic review was reported following the guidelines of the Preferred
Reporting Items for Systematic Reviews and Meta-analysis (PRISMA)22.
Protocol and registration
The systematic review protocol was registered at the International Prospective Register of
Systematic Reviews (PROSPERO) under the number CRD4201706783723.
Eligibility Criteria
- Inclusion Criteria
Studies that measured the frequency of deglutition disorders pre and post-treatment in
patients with head and neck neoplasms that received any type of therapy for the cancer
(surgery, chemotherapy, radiotherapy, or combination of therapies) were included. Only
studies with sample over 18 years old and those who had used image exams (i.e.
videofluoroscopy swallowing exam) as diagnostic criteria for assessment of deglutition
disorders and its complications were included. No language or period restriction was applied.
- Exclusion Criteria
Studies were excluded for the following reasons: (1) Patients without cancer or non-
malignant tumors; (2) Studies that did not use image exam (i.e. videofluoroscopy swallowing
exam or fiberoptic endoscopy evaluation) as diagnose criteria for deglutition disorders before
and after treatment for the cancer; (3) Patients that did not underwent any type of treatment/
therapy for the cancer; (4) Patients that are receiving treatment for the deglutition disorder/ or
23
only patients with dysphagia; (5) Studies that did not report values representative of the
deglutition disorders; (6) Reviews, letters, conference abstract, personal opinions, case
reports, cross sectional; (7) Full text not found; (8) Duplicated data from other study.
Information Sources
For the search in the literature, an individual strategy was developed for each of the
following databases: LILACS, PubMed, SpeechBITE, LIVIVO, Web of Science and Scopus.
An additional search of the grey literature was performed in the Google Scholar, OpenGrey,
and ProQuest. The search date was March 23th, 2017 in all the databases and grey literature.
The search strategies used are described in Appendix 1. The references cited in the included
articles were checked for any extra studies that could be included in the analysis as
recommended by Greenhalgh and Peacock24. The references were collected by the reference
manager software (EndNote™ Online Thomson Reuters, Philadelphia, PA). The duplicate
references were identified in this software and posteriorly any additional duplicate not
identified by EndNote, was found with the help of Rayyan qcri, a free web and mobile app for
systematic reviews (Qatar Computing Research Institute, Doha, Qatar)25.
Study Selection
The process of selection of the references was divided in two phases. The phase 1 was
performed by two reviewers (I.P.T and L.Q.P), who independently screened the title and
abstract of the collected references. This blind process was ensured and registered as it was
carried on the Rayyan qcri platform (Qatar Computing Research Institute, Doha, Qatar). The
studies that did not fit in the inclusion criteria were excluded. In the phase 2, the same
reviewers (I.P.T and L.Q.P) applied the eligibility criteria for the full text of the studies
selected after phase 1. When necessary, a third reviewer (K.F.L) was consulted to provide a
consensus between the two reviewers.
24
Data Collection Process
The first reviewer (I.P.T) collected the required information from the selected studies. The
second reviewer (L.Q.P) crosschecked all the collect information for accuracy. The data
collected consisted of: study characteristics (authors, year of publication, country, journal of
publication, type of study); population characteristics (sample size, age, type of cancer, cancer
stage); exposure characteristics (type of cancer treatment, deglutition assessment), and
outcome characteristics (occurrence of deglutition disorders pre-treatment and post-
treatment).
Risk of Bias in Individual Studies
The risk of bias of the individual studies was assessed by the JBI Critical Appraisal
Checklist for Studies Reporting Prevalence Data26. The first and second reviewers (I.P.T and
L.Q.P) performed this assessment independently. Any disagreements were solved by the
agreement of the three first reviewers (I.P.T, L.Q.P and K.F.L).
Analysis of subgroups
A subgroup analysis was performed by dividing the main findings by period: Pre cancer
treatment, up to 6 months post cancer treatment, and over 6 months post cancer treatment.
Also, the parameter aspiration was divided in three groups according cancer treatment
modality.
Summary measures
The data collected for the deglutition disorders or its complications
(aspiration/penetration) in adult patients with HNC that underwent cancer treatment were
expressed by mean percentage and its 95 percentage confidence intervals (95% CI).
Synthesis of results
A meta-analysis was planned within the studies that presented enough data of frequency
for deglutition disorders or its complications pre and post cancer treatment. These data were
25
analyzed by two types of meta-analysis, for fixed and random effects27. The calculus was
performed with the aid of MedCalc Statistical Software version 14.8.1 (MedCalc Software,
Ostend, Belgium). Heterogeneity was calculated by inconsistency indexes (I2), and a value
greater than 50% was considered and indicator of substantial heterogeneity within studies28. A
significance level was set at 5%.
RESULTS
Study selection
In phase one of this systematic review, 1368 records were screened from the main six
databases after removing the duplicates. Added to that, 302 records from the gray literature.
After screening all the titles and abstracts, 171 studies were selected for phase two, which
consists of full text screening. In the end of this phase, a total of 155 references were excluded
(Appendix 2). No additional articles were selected from the reference list. Therefore, sixteen
references were included for qualitative and quantitative analysis. All the selection process is
described in Figure 1.
Study characteristics
The sixteen16-21,29-38 articles included were published in ten different journals, a
fourth17,33,36,37 of them being published in the Head & Neck journal, three18,29,30 studies
published in the Dysphagia journal, and other two32,34 in the Laryngoscope journal. The
remaining seven studies were published in different oncology, medical or speech language
pathology journals. The total sample varied from 1132 to 13320 patients. Twelve16,19-21,30-34,36-38
of the included studies used the VFSS as diagnostic tool for deglutition disorders, two18,29
studies used the modified barium swallow (MBS), one17 study used the Fiberoptic endoscopic
evaluation of swallowing (FEES), and one35 study used the Videofluorographic exam. Almost
half18,31,32,33,35-37 of the studies were from the United States, two16,19 from Turkey, one from
Australia30, Canada38, China34, India29, Korea20, The Netherlands21, and United Kingdom17.
26
Because of the nature of the research question of this systematic review, all of the included
studies had a convenience sample. A summary of the characteristics of the sixteen studies can
be found in Table 1.
Risk of bias within studies
Nine17,19-21,29,33,36-38 of the included studies were classified as having low risk of bias.
Five18,30-32,34,35 other studies were considered as having moderate risk of bias, with five or six
of the ten questions in the assessment tool with “yes” answers. Only one16 study was assessed
as having high risk of bias. Question 2 (“Were study participant recruited in an appropriate
way?”) was the one where all of the studies answered “no”, that is because all of the samples
were of convenience nature. Almost half16,29-31,34,36 of the assessed studies answered “no” in
the ninth question (“Are all important confounding factors/ subgroups/ differences identified
and accounted for?”), which points out lack of information in the description of the sample
and/or selection criteria. All of the classification discrimination can be found in Appendix 3.
Results of included studies
Overall data distribution
All the samples in the included studies presented a higher distribution (at least two
thirds) towards the male sex. The most frequent type of cancer presented in the included
studies was oropharynx, followed by tongue, larynx, hypopharynx, nasopharynx, tonsil,
unknown sites, and others. Most of the studies that presented the data concerning cancers
stages had the samples grouped in the stages III-IV. Ten16,17,29-31,33-37 of the included studies
had as main treatment modality for cancer concurrent chemoradiotherapy. Other five18-20,32,38
studies showed that concerning modalities with surgery, conventional radiotherapy and/or
chemotherapy. Only 121 of the included studies presented data for the modality treatment of
Intensity-modulated radiation therapy (IMRT) combined with chemotherapy.
Pre-cancer treatment
27
All the sixteen included studies performed swallowing assessment with image exams
at the baseline. The type of parameters concerning deglutition was reported in different ways
across studies. The common parameter in fourteen16,17,19-21,29-31,32-36,38 of the included studies
was aspiration, a complication of deglutition disorders. The results of the meta-analysis at the
pre-cancer treatment showed a frequency of aspiration of 11.3% (Standard deviation (SD), 8.7
to 14.3%; total sample=517) (Figure 2a).
In six16,30,31 of the included studies was possible to analyze to total occurrence of
penetration of food, liquids or saliva above the vocal cords in the pre-cancer treatment period.
In the analyses, the frequency of penetration was of 14.7% (SD, 8.9 to 22.3%; total
sample=113) (Figure 2b).
Another important parameter that is related to deglutition disorders is the reduction of
the elevation of the larynx. The meta-analysis was possible for this parameter in four20,32,33,37
studies at the baseline. The frequency was established for this parameter at 14.1% (SD, 1.5 to
36.5%; total sample=204) (Figure 2c).
Up to 6 months post-cancer treatment
All the parameters analyzed in the period of time pre-cancer treatment were also
assessed from up to 6 months post-cancer treatment. In the meta-analysis of the aspiration,
thirteen16,17,19-21,29-31,32-36 of the fourteen studies included in the meta-analysis at baseline were
selected and presented a frequency of 27.1% (SD, 19.0 to 36.0%; total sample=478) (figure
2a). The frequency of penetration was of 37.1% (SD, 23.2 to 52.3%; total sample=113),
analyzed from six16,18,30,31,33,34 studies (figure 2b). Finally, the parameter reduced laryngeal
elevation had a frequency of 50.3% (SD, 15.3 to 85.1%; total sample=204), of a total of
four20,32,33,37 studies (figure 2c).
Over 6 months post-cancer treatment
28
Fewer studies were selected for the meta-analysis of the 3 parameters in the period
over 6 months post-cancer treatment. Many of the included studies did not follow the patient
over six months after receiving treatment for the cancer. For the analysis of aspiration, a total
of seven16,21,29-31,34,38 studies had data collected, only half as much as the baseline analysis.
The frequency of aspiration was of 17.9% (SD, 12.3 to 24.8%; total sample=153) (Figure 2a).
Similar to that, in the parameter penetration, only four16,30,31,34 studies included in the meta-
analysis had a prevalence of 33.2% (SD, 11.5 to 59.5%; total sample=80) (Figure 2b). And in
the third parameter, the reduction of larynx elevation, the frequency was not calculated
because none of the included studies had data for this parameter over six months post-cancer
treatment.
Aspiration by treatment modality
In the studies that reported data concerning aspiration up to 6 months post-cancer
treatment, nine16,17,29-31,33-36 used a combination of radiation therapy and chemotherapy as
treatment modality. In this group, there was a frequency of 23.8% of aspiration (SD, 14.2 to
35.0%; total sample=301). For the group that combined surgery, radiotherapy and/or
chemotherapy, three19,20,32 studies presented data of aspiration at the same period (up to 6
months post), and had a frequency of aspiration of 39.2% (SD, 22.0 to 57.9%; total
sample=138). Only one21 (16) study included had data concerning aspiration after treatment
using the modality IMRT and chemotherapy. This data was of the time period up to six
months post-cancer treatment and had a total of 16.3% of the sample of 55 patients with
aspiration. All this data is expressed in figure 2d.
Synthesis of results
A proportion meta-analysis was conducted within the 16 included studies. The data of
the analysis performed are grouped through figures 2a to 2d. The heterogeneity between the
studies varied from 19.8% to 95.4%, therefore a fixed or random model was chosen
29
depending on the heterogeneity result27. The higher frequency of the deglutition complication
was found in the period of up to 6 months post-cancer treatment. Aspiration was of 27.1%
(SD, 19.0 to 36.0%; total sample=478); penetration the higher frequency was of 37.1% (SD,
23.2 to 52.3%; total sample=113); and 50.3% (SD, 15.3 to 85.1%; total sample=204) for
reduced laryngeal elevation.
Level of evidence
The grading of recommendation, assessment, development, and evaluation system
(GRADE) for evaluating quality of evidence was adapted for the analysis of observational
studies and applied on three groups, according the meta-analysis performed for the deglutition
parameters before and after cancer treatment. The aspiration outcomes were evaluated as
moderate quality at baseline, low quality at up to 6 months post treatment, and as moderate
quality of evidence at over 6 months post treatment for HNC. The outcome penetration of
fluids above the vocal cords had a moderate quality of evidence at baseline and low quality at
1 to 6 months and over 6 months post cancer treatment. Reduced laryngeal elevation was the
only outcome that had moderate quality of evidence in both the baseline data and the up to 6
months post treatment. GRADE table of findings is shown on Appendix 4.
DISCUSSION
Approximately 30% of patients with HNC present with early disease (stage I or II)39.
In general, these patients are treated with either primary surgery or definitive radiation
therapy (RT)40. Locoregionally advanced (stage III/IV) HNC is associated with a high risk of
both local recurrence and distant metastases and requires combined modality approaches
(surgery, RT, and/or chemotherapy) for long-term disease control41. Radiotherapy is a crucial
part of HNC treatment, unfortunately it can cause several toxicities42.
Toxicity from cancer therapy is classified as acute or late based upon its temporal
relationship to treatment. Acute toxicity develops during or shortly after the completion of
30
treatment and is usually temporary. Late toxicity presents months to years after the
completion of treatment and is often permanent43. The most common long-term complication
of radiation therapy (RT) and chemoradiotherapy for HNC is xerostomia44. Late
complications may include lymphedema, carotid artery injury, trismus, thyroid disease and
dysphagia, among others44.
The objective of this systematic review (SR) was to assess the frequency of deglutition
disorders in the population of head and neck cancer patients. It was investigated deglutition
disorders parameters and complications that were diagnosed through image exams for the
swallowing function. The results found indicated a higher frequency of deglutition
complications in the period right after cancer treatments, from its completion up to six
months. It was also found a higher frequency of aspiration in the group of patients that went
through surgery, radiotherapy and/or chemotherapy as treatment for the HNC.
The data found in this SR, when compared to previous performed ones14,15 is
complementary and also sheds a different perspective in the swallowing complications in
HNC patients. The heterogeneity of the methodology of the studies published in the literature
was a common factor found in all three SR. However, the computing of key complications of
the swallowing process was possible to be analyzed in this review, showing when some
swallowing complications are more frequent.
Different types of swallowing impairments can be found in patients with HNC
previous and after cancer treatment. In the study by Lalla et al.45, it was reported through
quality of life questionnaire (OH-QOL), low scores towards the swallowing function, with the
aspect “chocking when swallowing” being worse at six months post treatment.
Some studies in the literature discuss that swallowing disorders, as dysphagia, has a
prevalence of 50.6%12 in the HNC population. Rinkel et al.46, with a sample of 50 patients, of
them 30 with oropharyngeal cancer, 79.0% presented swallowing problems after receiving
31
chemoradiation. In the USA, a population-based study found that over 9 million north
Americans reported swallowing problems, and that the third most common cause was HNC,
with 4.9%, in 201247.
A long term follow up of HNC patients after cancer treatment referred late dysphagia
for a median of nine years, with tube feeding present in 21.0% of the cases48. In a study of
over five years follow up of HNC survivors, 53.5% of patients treated with non-IMRT
modality and 22.0% in the IMRT treated group referred dysphagia49.
The findings in this systematic review points out that there is a higher prevalence of
the complication aspiration in the population that underwent surgery for the cancer and had
radiation and/or chemotherapy combined. In the study of Lindblom et al.50, 47% of the 108
patients analyzed through videoflouroscopic exam, aspirated. Of these patients, six had
pneumonia. For Mortensen et al.51, 18 out of 324 of the patients analyzed developed
aspiration pneumonia, more than half of that, 11 patients had been also diagnosed with
dysphagia.
LIMITATIONS
This systematic review had some limitations. The data collected for the parameters
analyzed were not from the same exact amount of studies or the exact period of time after
cancer treatment. This is even more evidenced when concerning the lack data for the
parameter reduced laryngeal elevation for the period over six months post cancer treatments.
Additionally, the parameter aspiration analyzed by different treatment modalities was
performed with different number of studies. For the modality IMRT there was only data from
one study, which makes the comparison more tenues.
CONCLUSIONS
The frequency of parameters or complications associated to deglutition disorders was
higher in the period immediate after cancer treatments (up to 6 months post-cancer treatment).
32
One of the most serious complications of deglutition disorders, the aspiration, had a frequency
of 27.1% in that period. The most frequent parameter was reduced laryngeal elevation, with
50.3%, in the same period of time as the aspiration one. However, for this parameter the
sample was smaller when compared to baseline and no study evaluated this elevation
reduction in the period over six months post-cancer treatment. This evidence presented in the
literature highlights the need for more longitudinal studies, which follow the patient for
periods longer than 12 months, with assessment of deglutition parameters through image
exams, and comparing these parameters through the different modalities of cancer treatment.
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30. Cartmill B, Cornwell P, Ward E, Davidson W, Porceddu S. A prospective investigation
of swallowing, nutrition, and patient-rated functional impact following altered
fractionation radiotherapy with concomitant boost for oropharyngeal cancer. Dysphagia.
2012;27(1):32-45. doi: 10.1007/s00455-011-9333-5.
36
31. Eisbruch A, Lyden T, Bradford CR, et al. Objective assessment of swallowing
dysfunction and aspiration after radiation concurrent with chemotherapy for head-and-
neck cancer. Int J Radiat Oncol Biol Phys. 2002;53(1):23-8.
32. Graner DE, Foote RL, Kasperbauer JL, et al. Swallow function in patients before and
after intra-arterial chemoradiation. Laryngoscope. 2003;113(3):573-9.
33. Kotz T, Costello R, Li Y, Posner MR. Swallowing dysfunction after chemoradiation for
advanced squamous cell carcinoma of the head and neck. Head Neck. 2004;26(4):365-72.
34. Ku PK, Yuen EH, Cheung DM, et al. Early swallowing problems in a cohort of patients
with nasopharyngeal carcinoma: Symptomatology and videofluoroscopic findings.
Laryngoscope. 2007;117(1):142-6.
35. Lazarus CL, Logemann JA, Pauloski BR, et al. Swallowing and tongue function
following treatment for oral and oropharyngeal cancer. J Speech Lang Hear Res.
2000;43(4):1011-23.
36. Logemann JA, Rademaker AW, Pauloski BR, et al. Site of disease and treatment protocol
as correlates of swallowing function in patients with head and neck cancer treated with
chemoradiation. Head Neck. 2006;28(1):64-73.
37. Logemann JA, Pauloski BR, Rademaker AW, et al. Swallowing disorders in the first year
after radiation and chemoradiation. Head Neck. 2008;30(2):148-58.
38. O'Connell DA, Rieger J, Harris JR, et al. Swallowing function in patients with base of
tongue cancers treated with primary surgery and reconstructed with a modified radial
forearm free flap. Arch Otolaryngol Head Neck Surg. 2008;134(8):857-64. doi:
10.1001/archotol.134.8.857.
39. Institute NC. Surveillance, Epidemiology and End Results 2017 [cited 2017
03/nov/2017]. Available from: <http://www.seer.cancer.gov>.
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40. Gregoire V, Lefebvre JL, Licitra L, Felip E. Squamous cell carcinoma of the head and
neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and
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Oncology / ESMO. 2010;21;5:184-6.
41. Al-Sarraf M. Treatment of locally advanced head and neck cancer: historical and critical
review. Cancer Control. 2002;9(5):387-99.
42. Gregoire V, Langendijk JA, Nuyts S. Advances in Radiotherapy for Head and Neck
Cancer. Journal of Clinical Oncology. 2015;33(29):3277-84.
43. Tolentino EdS, Centurion BS, Ferreira LHC, de Souza AP, Damante JH, Rubira-Bullen
IRF. Oral adverse effects of head and neck radiotherapy: literature review and suggestion
of a clinical oral care guideline for irradiated patients. Journal of Applied Oral Science.
2011;19(5):448-54.
44. Givens DJ, Karnell LH, Gupta AK, et al. Adverse events associated with concurrent
chemoradiation therapy in patients with head and neck cancer. Arch Otolaryngol Head
Neck Surg. 2009;135(12):1209-17. doi: 10.1001/archoto.2009.174
45. Lalla RV, Treister N, Sollecito T, et al.; OraRad Study Group. Oral complications at
6 months after radiation therapy for head and neck cancer. Oral Dis. 2017;23(8):1134-
1143. doi: 10.1111/odi.12710.
46. Rinkel RN, Verdonck-de Leeuw IM, Doornaert P, et al. Prevalence of swallowing and
speech problems in daily life after chemoradiation for head and neck cancer based on cut-
off scores of the patient-reported outcome measures SWAL-QOL and SHI. Eur Arch
Otorhinolaryngol. 2016;273(7):1849-55. doi: 10.1007/s00405-015-3680-z.
47. Bhattacharyya N. The prevalence of dysphagia among adults in the United States.
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48. Hutcheson KA, Lewin JS, Barringer DA, et al. Late dysphagia after radiotherapy-based
treatment of head and neck cancer. Cancer. 2012;118(23):5793-9. doi:
10.1002/cncr.27631.
49. Huang TL, Chien CY, Tsai WL, et al. Long-term late toxicities and quality of life for
survivors of nasopharyngeal carcinoma treated with intensity-modulated radiotherapy
versus non-intensity-modulated radiotherapy. Head Neck. 2016;38:1026-32. doi:
10.1002/hed.24150.
50. Lindblom U, Nilsson P, Gärskog O, et al. Aspiration as a late complication after
accelerated versus conventional radiotherapy in patients with head and neck cancer. Acta
Otolaryngol. 2016;136(3):304-11. doi: 10.3109/00016489.2015.1113439.
51. Mortensen HR, Jensen K, Grau C. Aspiration pneumonia in patients treated with
radiotherapy for head and neck cancer. Acta Oncol. 2013;52(2):270-6. doi:
10.3109/0284186X.2012.742205.
39
FIGURES LEGENDS
Figure 1. Flow diagram of literature search and selection criteria adapted from PRISMA22.
Figure 2a. Meta-analysis graphs and data for aspiration in three different periods.
Figure 2b. Meta-analysis graphs and data for penetration in three different periods.
Figure 2c. Meta-analysis graphs and data for reduced laryngeal elevation in two different
periods.
Figure 2d. Meta-analysis graphs and data for aspiration by type of cancer treatments.
40
Incl
ud
ed
Grey Literature
Google Scholar (n=69);
Open grey (n=6); ProQuest (n=227);
LILACS
(n=24)
PubMed
(n=559)
Scr
een
ing
Web of Science
(n=251)
Hand search of the reference list
Identified (n=1)
Included (n=0)
Scopus
(n=958)
Full-text article assessed in phase 2
(n=171)
Iden
tifi
cati
on
Records identified through first database searching
(n=1833)
Eli
gib
ilit
y
Records after duplicates removed
(n=1368)
Studies excluded with reasons
(n=155):
(1) Patients without cancer or non-malignant
tumors (n=4);
(2) Studies that did not use VFSE, MBS or FEES
(image exam) as diagnose criteria for deglutition
disorders before and after treatment for the cancer
(n=81);
(3) Patients that did not underwent any type of
treatment/ therapy for the cancer (n=3);
(4) Patients that are receiving treatment for the
deglutition disorder/ or only patients with
dysphagia (n=4);
(5) Studies that did not report values
representative of the deglutition disorders (n=37);
(6) Reviews, letters, conference abstract, personal
opinions, case reports, cross sectional,
experimental (n=12);
(7) Full text not found (n=13);
(8) Duplicated data that used sample and results
from other study (n=1).
LIVIVO
(n=36)
Studies included in Qualitative and Quantitative synthesis
(n=16)
SpeechBite
(n=5)
41
42
43
44
45
Table 1. Summary of study descriptive characteristics of included studies (n=16).
Author,
year,
country
Type
of
study
Sampl
e size
(M:F)
Mean
age or
age
range
(years)
Type of cancer (n) Tumo
r
stages
(n)
Type of cancer
treatment (n)
Deglutition
assessment
(period)
Occurrence of deglutition disorders (n)
Pretreatment < 6 months of
treatment
>6 months of
treatment
Agarwal et
al., 2011,
India
Cohor
t
47
(40:7)
40-65 Oropharynx (25*)
Hypopharynx (16*)
I/II
(11)
III/IV
(36)
-Conventional
RT 66-70 Gy/33-
35 fractions (40)
-Conformal RT
(7)
-Concurrent CT
cisplatin (40)
MBS (before
and up to 12
months
posttreatment
)
-Aspiration=9
of 47
-PAS=0
2 months post:
-Aspiration=11
of 46
-PAS=13 of 34
-6 months after:
-Aspiration=11
of 38
-PAS=9 of 30
12 months post:
-Aspiration= 5
of 17
-PAS=10 of 14
Cartmill et
al., 2012,
Australia
Cohor
t
14
(12:2)
53-82 Tonsil (9)
Supraglottis (3)
I (2*)
II (4*)
III (5*)
IV
(3*)
-AFRT-CB 66
Gy/35 fractions
(14)
VFSS (before
and up to 6
months
posttreatment
)
-Aspiration on
fluids/solids =
0/1
-Penetration on
fluids/solids =
1/ 3
-PAS=5 events
4-6 weeks post
=
-Aspiration on
fluids/solids =
1/1
-Penetration on
fluids/solids =
3/ 3
-PAS=8 events
6 months post =
-Aspiration on
fluids/solids =
1/2
-Penetration on
fluids/solids =
1/ 4
-PAS=8 events
Eisbruch et
al., 2002,
USA
Cohor
t
26
(NA)
NA Oropharynx (14)
Nasopharynx (4)
Oral cavity (2)
Larynx (2)
Hypopharyngeal (1)
Thyroid (1)
Paranasal sinus (1)
External ear (1)
III/IV
(26)
-Conventional
RT 70 Gy/35
fractions for
Primary tumor;
50-54 Gy or 58-
64 Gy for
metastasis or
previous to
surgery (26)
-Concurrent QT
gemcitabine (26)
VFSS (before
and up to 12
months
posttreatment
)
-Base of tongue
weakness=9
-Pharyngeal
residue=5
-Reduced
larynx/hyoid
elevation=4
-Reduced
epiglottic
inversion=3
-Swallow reflex
delay=8
-
1-3 months
post:
-Base of tongue
weakness=11
-Pharyngeal
residue=15
-Reduced
larynx/hyoid
elevation=7
-Reduced
epiglottic
inversion=10
-Swallow reflex
6-12 months
post:
-Base of tongue
weakness=11
-Pharyngeal
residue=10
-Reduced
larynx/hyoid
elevation=6
-Reduced
epiglottic
inversion=7
-Swallow reflex
46
Velopharyngeal
incompetence=
1
-
Cricopharyngea
l m.
dysfunction=0
-Upper
esophageal
stricture=2
-Penetration=4
-Aspiration=1
-Silent
aspiration=2
delay=6
-
Velopharyngeal
incompetence=
5
-
Cricopharyngea
l m.
dysfunction=1
-Upper
esophageal
stricture=7
-Penetration=5
-Aspiration=10
-Silent
aspiration=3
delay=8
-Velopha
ryngeal
incompetence=
2
-Cricopha
ryngeal m.
dysfunction=1
-Upper
esophageal
stricture=6
-Penetration =3
-Aspiration =5
-Silent
aspiration=3
Erkal et al.,
2014,
Turkey
Cohor
t
20
(17:3)
30-76 Nasopharynx (10)
Supraglottic larynx
(10)
NA -3DCRT 70 Gy
for the primary
tumor; 66-70 Gy
involved cervical
lymph nodes; 50-
60 Gy
uninvolved
cervical lymph
nodes; 46-50Gy
supraclavicular
lymph nodes/
daily fractions 2
Gy (8)
-3DCRT with
Concomitant CT
(12)
VFSS (before
and up to 6
months
posttreatment
)
-Impaired
lingual
movement=1
-Base of tongue
weakness=10
-Pharyngeal
residue=7
-Reduced
laryngeal
elevation=2
-Reduced
epiglottic
inversion=0
-Swallow reflex
delay=0
-
Cricopharyngea
l muscle
dysfunction=0
-Proximal
esophageal
stricture=3
At 3 months
post:
-Impaired
lingual
movement=4
-Base of tongue
weakness=15
-Pharyngeal
residue=11
-Reduced
laryngeal
elevation=2
-Reduced
epiglottic
inversion=6
-Swallow reflex
delay=1
-
Cricopharyngea
l muscle
dysfunction=2
-Proximal
At 6 months
post:
-Impaired
lingual
movement=2
-Base of tongue
weakness=12
-Pharyngeal
residue=10
-Reduced
laryngeal
elevation=3
-Reduced
epiglottic
inversion=5
-Swallow reflex
delay=1
-Cricophary
ngeal muscle
dysfunction=2
-Proximal
esophageal
47
-Penetration=5
-Aspiration=0
esophageal
stricture=5
-Penetration=10
-Aspiration=1
stricture=6
-Penetration
=14
-Aspiration =4
Graner et
al., 2003,
USA
Cohor
t
11
(7:4)
37-78 Oropharynx (5)
Larynx (3)
Hypopharynx (3)
III-IV
(11)
-CT 150 mg/m2
of cisplatin for 4
weeks (11)
-Concomitant RT
72 Gy, 6 weeks
for primary
tumor (11)
-Surgery (select,
modified or
radical neck
dissection= 7)
VFSS (before
and up to 5
months
posttreatment
)
-Oral residue=0
-Nasal
regurgitation=0
-Diffuse falling
over tongue
base=1
-Delayed
pharyngeal
response=3
-Reduced
tongue base
retraction=5
-Reduced
Laryngeal
elevation=5
-Laryngeal
vestibule, thin
liquid=6
-Laryngeal
vestibule, thick
liquid=6
-Laryngeal
vestibule,
pureed=1
-Aspiration=3
-Valleculae
residue, thin
liquid=3
-Valleculae
residue, thick
liquid=6
-Valleculae
residue,
pureed=3
-Pyriform sinus
At 5 months
post:
-Oral residue=1
-Nasal
regurgitation=1
-Diffuse falling
over tongue
base=0
-Delayed
pharyngeal
response=4
-Reduced
tongue base
retraction=9
-Reduced
Laryngeal
elevation=9
-Laryngeal
vestibule, thin
liquid=9
-Laryngeal
vestibule, thick
liquid=9
-Laryngeal
vestibule,
pureed=5
-Aspiration=7
-Valleculae
residue, thin
liquid=7
-Valleculae
residue, thick
liquid=10
-Valleculae
residue,
NA
48
residue, thin
liquid=1
-Pyriform sinus
residue, thick
liquid=3
-Pyriform sinus
residue,
pureed=3
-Tight
cricopharyngeal
segment=2
Backflow to
pharynx=1
pureed=7
-Pyriform sinus
residue, thin
liquid=8
-Pyriform sinus
residue, thick
liquid=8
-Pyriform sinus
residue,
pureed=4
-Tight
cricopharyngeal
segment=4
Backflow to
pharynx=1
Kotz et al.,
2004, USA
Cohor
t
12
(9:3)
31-72 Oropharynx (7)
Larynx (3)
Oral cavity (1)
Unknow (1)
III-IV
(12)
-Induction CT 2-
3 cycles
-CT Docetaxel
during 4 weeks
of RT and 3
weeks of
Hyperfractionate
d RT (5)
-CT Carboplatin
6-7 weeks and
once-a-day RT
(7)
VFSS (before
and 1-4
weeks
posttreatment
)
-Reduced
tongue base to
posterior
pharyngeal
wall=1*
-Reduced
laryngeal
elevation=1*
-Reduced
laryngeal
vestibule
closure=1*
-Reduced upper
esophageal
sphincter
opening=0
-Reduced
tongue base to
posterior
pharyngeal
wall=12*
-Reduced
laryngeal
elevation=10*
3ml/ 11* 5ml
-Reduced
laryngeal
vestibule
closure=9* 3ml/
8* 5ml
-Reduced upper
esophageal
sphincter
opening=2*
-Laryngeal
aspiration=4
-Penetration=9
NA
Ku et al.,
2007, China
Cohor
t
20
(14:6)
33-62 Nasopharyngeal
carcinoma (20)
I-II (9)
III-IV
(11)
-RT 66 Gy (20)
-RT boost of 20
Gy for
VFSS (before
and up to 12
months
-Impaired
lingual
control=0
At 6 months
post:
-Impaired
At 12 months
post:
-Impaired
49
pharyngeal
extension (17)
-Concurrent CT
cisplatin (11)
posttreatment
)
-Impaired oral
transfer food=0
-Stasis in
Vallecula=0
-Stasis in
pyriform
fossa=0
-Impaired
pharyngeal
peristalsis=3*
-Impaired
tongue
propulsion=1*
-Penetration=
2*
-Aspiration=2*
lingual
control=8*
-Impaired oral
transfer
food=9*
-Stasis in
Vallecula=17*
-Stasis in
pyriform
fossa=12*
-Impaired
pharyngeal
peristalsis=12*
-Impaired
tongue
propulsion=3*
-Penetration=
7*
-Aspiration=0
lingual
control=8*
-Impaired oral
transfer
food=8*
-Stasis in
Vallecula=20*
-Stasis in
pyriform
fossa=12*
-Impaired
pharyngeal
peristalsis=12*
-Impaired
tongue
propulsion=6*
-Penetration
=5*
-Aspiration =1*
Lazarus et
al., 2000,
USA
Cohor
t
13
(10:3)
38-72 Tongue base (6)
Floor of the mouth
(3)
Tonsil (4)
I (1)
IV
(12)
-RT high dose
≥7000 cGy (13)
-Concomitant CT
cisplatin (12)
VFG
(before and
up to 2
months
posttreatment
)
-Aspiration=1 At 2 months
post:
-Aspiration=7
NA
Logemann
et al., 2006,
USA
Cohor
t
53
(41:12)
NA Oropharynx (22)
Larynx (14)
Hypopharynx (4)
Nasopharynx (3)
Unknown (10)
T1 (2)
T2
(11)
T3
(16)
T4
(19)
IV
(42-
53*)
-TFHX, Taxol
infusion (13)
-TFHX, Taxol
bolus (16)
-TFHX, bolus,
induction (15)
-RADPLAT (9)
-RT dose range
6700-7275 cGy
(53)
VFSS (before
and up to 3
months
posttreatment
)
-Reduced
Tongue base
retraction=26*
-Reduced
tongue
strength=20*
-Delayed
laryngeal
vestibule
closure=10*
-Reduced
tongue
control=9*
-Delayed
At 3 months
post:
-Reduced
Tongue base
retraction=47*
-Reduced
tongue
strength=27*
-Delayed
laryngeal
vestibule
closure=16*
-Reduced
lateral/anterior
NA
50
pharyngeal
swallow=8*
-Reduced
laryngeal
elevation=7*
-Reduced
propulsion of
bolus=6*
-Reduced
tongue
stabilization=3*
-Bilateral
pharyngeal
weakness=3*
-Reduced
vertical tongue
movement=2*
-Reduced
cricopharyngeal
opening=1*
-Visible
cricopharyngeal
bar=1*
-Unilateral
pharyngeal
weakness=1*
-Gastrostomy or
jejunostomy=8
-Aspiration=4
tongue
Stabilization=2
*
-Incomplete
laryngeal
vestibule
Closure=2*
-Reduced
velopharyngeal
closure=2*
-Reduced
vertical tongue
movement=1*
-Reduced
glottic
closure=0*
-Gastrostomy or
jejunostomy=21
-Aspiration=12
Logemann
et al., 2008,
USA
Cohor
t
48
(38:10)
38-76 Oropharynx (21)
Laryngeal (21)
Nasopharynx (3)
Hypopharynx (3)
I (1)
II (7)
III-IV
(40)
-CT (36)
-Concurrent RT
dose range from
6500 to 7920
cGy (36)
-Induction CT (6)
-RT dose range
from 6500 to
7920 cGy (12)
VFSS (before
and up to 12
months
posttreatment
)
-Reduced
tongue base
retraction=32*
-Reduced
tongue
strength=24*
-Delay in
triggering the
pharyngeal
swallow=19*
At 3 months
post:
-Reduced
tongue base
retraction=43*
-Reduced
tongue
strength=29*
-Delay in
triggering the
At 12 months
post:
-Reduced
tongue base
retraction= 41*
-Reduced
tongue
strength= 27*
-Delay in
triggering the
51
-
Slowed/delayed
vestibule
closure=13*
-Reduced
tongue
control=16*
-Reduced
Anterior-
Posterior
tongue
movement=12*
-Reduced
laryngeal
elevation=8*
-Reduced
tongue
stabilization=7*
-Bilateral
pharyngeal
weakness=4*
-Reduced
cricopharyngeal
opening=4*
-Visible
cricopharyngeal
bar=5*
-Incomplete
laryngeal
vestibule
closure=3
pharyngeal
swallow=27*
-
Slowed/delayed
vestibule
closure=29*
-Reduced
tongue
control=22*
-Reduced
Anterior-
Posterior
tongue
movement=22*
-Reduced
laryngeal
elevation=15*
-Reduced
tongue
stabilization=6*
-Bilateral
pharyngeal
weakness=11*
-Reduced
cricopharyngeal
opening=11*
-Visible
cricopharyngeal
bar=6*
-Incomplete
laryngeal
vestibule
closure=6*
pharyngeal
swallow= 20*
-Slowed/
delayed
vestibule
closure=26*
-Reduced
tongue
control=18*
-Reduced
Anterior-
Posterior
tongue
movement=27*
-Reduced
laryngeal
elevation= 17*
-Reduced
tongue
stabilization=7*
-Bilateral
pharyngeal
weakness= 10*
-Reduced
cricopharyngeal
opening= 10*
-Visible
cricopharyngeal
bar=7*
-Incomplete
laryngeal
vestibule
closure=6*
O’Connell
et al., 2008,
Canada
Cohor
t
20
(14:6)
44-70 Base of tongue (20) II (2)
III (8)
IV
(10)
-Primary Surgery
and
reconstruction
with beavertail
modification of
the radial forearm
VFSS (before
and at 12
months
posttreatment
)
-Mild
pharyngeal
residue
During=17
-Moderate
pharyngeal
NA At 12 months
post:
-Mild
pharyngeal
residue
During=6
52
free flap (20)
-Postoperative
RT (20)
-Primary CT and
RT (5)
residue=3
-Aspiration=0
-Moderate
pharyngeal
residue=6
-Severe
pharyngeal
residue=8
-Aspiration= 1
Patterson et
al., 2014,
United
Kingdom
Cohor
t
112
(90:22)
42-77 Oropharynx (59)
Hypopharynx (22)
Larynx (16)
Nasopharynx (5)
Unknown (10)
NA -RT 3D
conformal, dose
63Gy in 30
fractions over 6
weeks (112)
-Combined CT
Cisplatin
40mg/m2 in 6
cycles or
Mitomycin C
15mg/m2 in 2
cycles (112)
FEES (before
and at 3
months
posttreatment
)
-Aspiration=10
of 112 patients
At 3 months
post:
-
Aspiration=27*
of 97 patients
-Silent
aspiration=8*
of 97 patients
NA
Rogus-
Pulia et al.,
2014, USA
Cohor
t
21
(17:4)
36-80 Base of tongue (8)
Tonsil (6)
Nasopharynx (3)
Hypopharynx (1)
Tongue (1)
Vocal Fold (1)
Unknown (1)
T0 (2)
T1 (6)
T2 (9)
T4 (4)
I-IV
(21)
-RT dose of 66 to
70 Gy over a
mean of 7 weeks
(21)
-Concurrent CT
(21)
-Induction CT (6)
-Tonsillectomy
(4)
-Neck dissection
(3)
-Partial
Glossectomy (1)
-Tumor
debulking (1)
MBS (before
and mean of 5
months
posttreatment
)
-Penetration
during
swallow=2
Mean of 5
months post:
-Penetration
during
swallow=6
NA
Serel et al.,
2013,
Turkey
Cohor
t
40
(33:7)
20-65 Larynx (20)
Nasopharynx (5)
Tongue (5)
Tonsil (3)
Retromolar trigone
I (5)
II (1)
IIA (2)
IIB (1)
III (20)
-RT dose from
5400 cGy to
7000 cGy (40)
-Concomitant CT
(33)
VFSS (before
and up to 3
months
posttreatment
)
-Aspiration
with liquid=2
-Aspiration
with pudding=0
-Aspiration
At 1 month
post:
-Aspiration
with liquid=8
-Aspiration
NA
53
(2)
Parotid (2)
Lips (1)
Tongue base (1)
Hypopharynx (1)
IVA
(11)
-Surgery for the
primary tumor
(2)
-Surgery for the
primary tumor
and neck
dissection (24)
with biscuit=0 with pudding=7
-Aspiration
with biscuit=7
At 3 months
post:
-Aspiration
with liquid=9
-Aspiration
with pudding=7
-Aspiration
with biscuit=7
Son et al.,
2015,
Korea
Cohor
t
133
(85:48)
53.5±1
5
Tongue (133) T1
(38)
T2
(40)
T3 (3)
T4
(52)
-Hemiglossec
tomy (16)
-Wide resection
(82)
-Partial
glossectomy (23)
-Total
glossectomy (5)
-Supraomohyoid
neck dissection
(61)
-Modified radical
neck dissection
(59)
-Reconstruction
surgery (81)
-RT (70)
-CT (57)
VFSS (was
administered
to 87 patients
after surgery
and to 74
patients prior
to surgery -
before and
mean of 4
months
posttreatment
)
-Inadequate lip
movement=0
-Inadequate
tongue
control=18
-Inadequate
chewing=5
-Delayed oral
transit time=3
-Aspiration or
penetration=8
-Fluid
aspiration=15
-Solid
aspiration=5
-Nasal
regurgitation=0
-Vallecular
pouch
residue=6
-Pyriform sinus
residue=3
-Inadequate
laryngeal
elevation=1
At mean of 4
months post:
-Inadequate lip
movement=3
-Inadequate
tongue
control=64
-Inadequate
chewing=25
-Delayed oral
transit time=28
-Aspiration or
penetration=26
-Fluid
aspiration=36
-Solid
aspiration=15
-Nasal
regurgitation=4
-Vallecular
pouch
residue=39
-Pyriform sinus
residue=16
-Inadequate
laryngeal
elevation=12
NA
Van der Cohor 55 32-79 Oral III (17) CT-IMRT VFSS (before -Aspiration At 10 weeks At 12 months
54
Molen et
al., 2013,
The
Netherland
s
t (44:11) cavity/Oropharynx
(29)
Laryngo/hypopharyn
x (19)
Nasopharynx (7)
IV
(38)
Cisplatin
100mg/m2 (40
minutes for 3
non-consecutive
days); 70 Gy in
35 daily fractions
of 2Gy – total of
7000 cGy over 7
weeks plus
sequential boost
of IMRT (55).
– 55 patients/
at 10 weeks-
48 patients/ at
12 months-36
patients)
and/or
penetration=9
of 55
post:
-Aspiration
and/or
penetration=8
of 39
post:
-Aspiration
and/or
penetration=5
of 36
Legend: MBS = modified barium swallow; M = male; F = female; RT = radiotherapy; CT = chemotherapy; CRT = chemoradiation; AFRT-CB = altered fractionation radiotherapy
with concomitant boost; IMRT = intensity-modulated radiotherapy; VFSS = videofluroscopy; VFG = Videofluorographic; FEES=Fiber-optic endoscopic evaluation of swallowing;
PAS= penetration-aspiration scale (only values with grade 3 or over); Events = number of events of penetration/aspiration; RADPLAT= intraarterial cisplatin radiation; TFHX, Taxol
infusion= hydroxyurea, 5-fluorouracil, and paclitaxel infusion for 1 week; TFHX, Taxol bolus= hydroxyurea, 5-fluorouracil, and paclitaxel 1-hour bolus; TFHX, bolus, induction=
induction chemotherapy with carboplatin and paclitaxel followed by concurrent chemoradiation with hydroxyurea, 5-fluorouracil, and paclitaxel 1-hour bolus; NA = Not Available.
*Values calculated by the author
55
Appendix 1. Search strategy and date that was performed in the chosen Databases.
Databa
se
Search
(March 23, 2017)
LILA
CS
(tw:(Cancer OR câncer OR neoplasia OR Neoplasm OR tumor)) AND
(tw:(Disfagia OR dysphagia OR “alteração de deglutição” OR “swallowing
disorders” OR “disfunción de deglución”)) AND (tw:(Quimioterapia OR
chemotherapy OR radioterapia OR radiotherapy OR quimioradioterapia OR
chemoradiotherapy OR quimiorradioterapia))
PubMe
d
#1: "Neoplasms"[Mesh] OR cancer OR cancers OR neoplasm OR "neoplasms" OR
tumor OR tumors OR tumour OR tumours OR neoplasia OR "malignant neoplasm"
OR "malignant tumour" OR "malignant tumor" OR "malignant tumors" OR
"malignant tumours" OR carcinoma OR carcinomas
#2: "Deglutition Disorders"[Mesh] OR "Respiratory Aspiration"[Mesh] OR
aspiration OR "food aspiration" OR "liquid aspiration” OR "Aspiration Pneumonia"
OR "Aspiration Pneumonias" OR dysphagia OR "swallowing disorders" OR
"swallowing problems" OR "swallowing difficulties" OR "swallowing impairment"
OR "deglutition disorder" OR "deglutition disorders" OR "swallowing disorder"
OR "oropharyngeal dysphagia" OR "esophageal dysphagia" OR "mechanical
dysphagia"
#3: "clinical examination" OR "clinical exam" OR "clinical assessment" OR
"swallowing exam" OR "swallowing assessment" OR "video fluoroscopic" OR
"VFSE" OR "VFSS" OR "VSF" OR "videofluoroscopy"
#4: "Radiotherapy"[Mesh] OR "Chemoradiotherapy"[Mesh] OR surgery OR
chemotherapy OR chemotherapies OR "radiotherapy" OR radiotherapies OR
"radiation therapy" OR "radiation therapies" OR "targeted radiotherapy" OR
"targeted radiotherapies" OR "targeted radiation therapy" OR "targeted radiation
therapies" OR chemoradiotherapy OR chemoradiotherapies OR
"radiochemotherapy" OR "radiochemotherapies" OR "combination therapy" OR
"tumor removal" OR "cancer therapy" OR "cancer treatment" OR "tumor resection"
OR "tumour resection" OR "tumour removal"
#5: #1 AND #2 AND #3 AND #4
Scopus
TITLE-ABS-
KEY ( cancer OR cancers OR neoplasm OR "neoplasms" OR tumor OR tumo
rs OR tumour OR tumours OR neoplasia OR "malignant
neoplasm" OR "malignant tumour" OR "malignant tumor" OR "malignant
tumors" OR "malignant
tumours" OR carcinoma OR carcinomas ) AND TITLE-ABS-KEY ( "Respiratory
aspiration" OR aspiration OR "food aspiration" OR "liquid
aspiration" OR "Aspiration Pneumonia" OR "Aspiration
Pneumonias" OR dysphagia OR "swallowing disorders" OR "swallowing
problems" OR "swallowing difficulties" OR "swallowing
56
impairment" OR "deglutition disorder" OR "deglutition
disorders" OR "swallowing disorder" OR "oropharyngeal
dysphagia" OR "esophageal dysphagia" OR "mechanical
dysphagia" ) AND TITLE-ABS-KEY ( "clinical examination" OR "clinical
exam" OR "clinical assessment" OR "swallowing exam" OR "swallowing
assessment" OR "video
fluoroscopic" OR "VFSE" OR "VFSS" OR "VSF" OR "videofluoroscopy" ) AN
D TITLE-ABS-
KEY ( surgery OR chemotherapy OR chemotherapies OR "radiotherapy" OR r
adiotherapies OR "radiation therapy" OR "radiation therapies" OR "targeted
radiotherapy" OR "targeted radiotherapies" OR "targeted radiation
therapy" OR "targeted radiation
therapies" OR chemoradiotherapy OR chemoradiotherapies OR "radiochemoth
erapy" OR "radiochemotherapies" OR "combination therapy" OR "tumor
removal" OR "cancer therapy" OR "cancer treatment" OR "tumor
resection" OR "tumour resection" OR "tumour removal" ) AND ( LIMIT-
TO ( DOCTYPE , "ar" ) OR LIMIT-TO ( DOCTYPE , "sh" ) OR LIMIT-
TO ( DOCTYPE , "ip" ) )
Web of
Scienc
e
#1: TS=(cancer OR cancers OR neoplasm OR "neoplasms" OR tumor OR tumors
OR tumour OR tumours OR neoplasia OR "malignant neoplasm" OR "malignant
tumour" OR "malignant tumor" OR "malignant tumors" OR "malignant tumours"
OR carcinoma OR carcinomas)
#2: TS=("Respiratory aspiration" OR aspiration OR "food aspiration" OR "liquid
aspiration" OR "Aspiration Pneumonia" OR "Aspiration Pneumonias" OR
dysphagia OR "swallowing disorders" OR "swallowing problems" OR "swallowing
difficulties" OR "swallowing impairment" OR "deglutition disorder" OR
"deglutition disorders" OR "swallowing disorder" OR "oropharyngeal dysphagia"
OR "esophageal dysphagia" OR "mechanical dysphagia")
#3: TS=("clinical examination" OR "clinical exam" OR "clinical assessment" OR
"swallowing exam" OR "swallowing assessment" OR "video fluoroscopic" OR
"VFSE" OR "VFSS" OR "VSF" OR "videofluoroscopy")
#4: TS=(surgery OR chemotherapy OR chemotherapies OR "radiotherapy" OR
radiotherapies OR "radiation therapy" OR "radiation therapies" OR "targeted
radiotherapy" OR "targeted radiotherapies" OR "targeted radiation therapy" OR
"targeted radiation therapies" OR chemoradiotherapy OR chemoradiotherapies OR
"radiochemotherapy" OR "radiochemotherapies" OR "combination therapy" OR
"tumor removal" OR "cancer therapy" OR "cancer treatment" OR "tumor resection"
OR "tumour resection" OR "tumour removal")
#5: #1 AND #2 AND #3 AND #4
LIVIV
O
TI=((cancer OR cancers OR neoplasm OR "neoplasms" OR tumor OR tumors OR
tumour OR tumours OR neoplasia OR "malignant neoplasm" OR "malignant
tumour" OR "malignant tumor" OR "malignant tumors" OR "malignant tumours"
OR carcinoma OR carcinomas)) AND TI=(("Respiratory aspiration" OR aspiration
OR "food aspiration" OR "liquid aspiration" OR "Aspiration Pneumonia" OR
"Aspiration Pneumonias" OR dysphagia OR "swallowing disorders" OR
57
"swallowing problems" OR "swallowing difficulties" OR "swallowing impairment"
OR "deglutition disorder" OR "deglutition disorders" OR "swallowing disorder"
OR "oropharyngeal dysphagia" OR "esophageal dysphagia" OR "mechanical
dysphagia")) AND TI=(("clinical examination" OR "clinical exam" OR "clinical
assessment" OR "swallowing exam" OR "swallowing assessment" OR "video
fluoroscopic" OR "VFSE" OR "VFSS" OR "VSF" OR "videofluoroscopy")) AND
TI=((surgery OR chemotherapy OR chemotherapies OR "radiotherapy" OR
radiotherapies OR "radiation therapy" OR "radiation therapies" OR "targeted
radiotherapy" OR "targeted radiotherapies" OR "targeted radiation therapy" OR
"targeted radiation therapies" OR chemoradiotherapy OR chemoradiotherapies OR
"radiochemotherapy" OR "radiochemotherapies" OR "combination therapy" OR
"tumor removal" OR "cancer therapy" OR "cancer treatment" OR "tumor resection"
OR "tumour resection" OR "tumour removal"))
Speech
BITE
Keyword(s): cancer AND dysphagia
Practice Area: Dysphagia
Within population: Cancer
Research Design: Non Randomised Controlled Trial
Schola
r
Search 1: tudonotítulo: cancer swallowing radiotherapy chemotherapy
Search 2: tudonotítulo: cancer swallowing radiotherapy
Search 3: tudonotítulo: cancer swallowing chemotherapy
Openg
rey
Cancer AND Swallowing
ProQu
est
TI,AB(cancer OR cancers OR neoplasm OR "neoplasms" OR tumor OR tumors OR
tumour OR tumours OR neoplasia OR "malignant neoplasm" OR "malignant
tumour" OR "malignant tumor" OR "malignant tumors" OR "malignant tumours"
OR carcinoma OR carcinomas) AND TI,AB("Respiratory aspiration" OR aspiration
OR "food aspiration" OR "liquid aspiration" OR "Aspiration Pneumonia" OR
"Aspiration Pneumonias" OR dysphagia OR "swallowing disorders" OR
"swallowing problems" OR "swallowing difficulties" OR "swallowing impairment"
OR "deglutition disorder" OR "deglutition disorders" OR "swallowing disorder"
OR "oropharyngeal dysphagia" OR "esophageal dysphagia" OR "mechanical
dysphagia") AND TI,AB("clinical examination" OR "clinical exam" OR "clinical
assessment" OR "swallowing exam" OR "swallowing assessment" OR "video
fluoroscopic" OR "VFSE" OR "VFSS" OR "VSF" OR "videofluoroscopy") AND
TI,AB(surgery OR chemotherapy OR chemotherapies OR "radiotherapy" OR
radiotherapies OR "radiation therapy" OR "radiation therapies" OR "targeted
radiotherapy" OR "targeted radiotherapies" OR "targeted radiation therapy" OR
"targeted radiation therapies" OR chemoradiotherapy OR chemoradiotherapies OR
"radiochemotherapy" OR "radiochemotherapies" OR "combination therapy" OR
"tumor removal" OR "cancer therapy" OR "cancer treatment" OR "tumor resection"
OR "tumour resection" OR "tumour removal")
Appendix 2. Excluded articles and reasons for exclusion (n=155).
58
Author, year Reason for exclusion
Al-Othman et al., 2003(1) 2
Andrade et al., 2017(2) 2
Angelis et al., 2003(3) 2
Aplak et al., 2007(4) 2
Archontaki et al., 2010(5) 2
Arrese et al., 2017(6) 5
Atkins et al., 2006(7) 1
Barringer et al., 2009(8) 5
Barros et al., 2007(9) 7
Batth et al., 2014(10) 6
Bergquist et al., 2007(11) 2
Bodin et al., 2004(12) 5
Borggreven et al., 2007(13) 2
Brookes et al., 2006(14) 5
Bruijn et al., 2013(15) 6
Bumber et al., 1990(16) 5
Caglar et al., 2007(17) 7
Caliceti et al., 2004(18) 5
Campbell et al., 2004(19) 2
Carnaby et al., 2014(20) 2
Cartmill et al., 2011(21) 7
Celedon et al., 2008(22) 2
Chan et al., 2009(23) 7
Chang et al., 2003(24) 2
Chone et al., 2011(25) 5
Christianen et al., 2016(26) 5
Cintra et al., 2005(27) 2
Coia et al., 1993(28) 2
Collan et al., 2011(29) 5
Crombie et al., 2015(30) 5
Dale et al., 2016(31) 2
Del Bon et al., 2012(32) 6
Deng et al., 2009(33) 2
Deng et al., 2016(34) 6
Dracini et al., 2013(35) 2
Eisbruch et al., 2004(36) 8
Eisbruch et al., 2011(37) 2
Fang et al., 2004(38) 2
Ford et al., 2009(39) 2
Frowen et al., 2010(40) 5
Frowen et al., 2016(41) 5
Garcia-Peris et al., 2007(42) 2
Gaspar et al., 2000(43) 2
Gluck et al., 2010(44) 5
Haderlein et al., 2014(45) 2
Halczy-Kowalik et al., 2015(46) 2
Hara et al., 2003(47) 2
Hartl et al., 2010(48) 5
59
Hey et al., 2013(49) 2
Higo et al., 2011(50) 6
Hughes et al., 2000(51) 2
Hunter et al., 2013(52) 2
Hunter et al., 2014(53) 5
Hutcheson et al., 2015(54) 6
Itoh et al., 2015(55) 2
Jacob et al., 1998(56) 2
Jensen et al., 2007(57) 2
Jung et al., 2011(58) 3
Kato et al., 2007(59) 5
Kendall et al., 1998(60) 5
Knox et al., 2010(61) 2
Kolh et al., 1998(62) 7
Kraaijenga et al., 2015(63) 2
Kreeft et al., 2012(64) 5
Kreuzer et al., 2000(65) 2
Kumar et al., 2014(66) 2
Kurnatowski et al., 2014(67) 2
Kurosu et al., 2011(68) 4
Langendijk et al., 2009(69) 2
Lazarus et al., 1996(70) 2
Lazarus et al., 2007(71) 5
Leder et al., 1998(72) 2
Lee et al., 2016(73) 2
Leu et al., 2005(74) 2
Lewin et al., 2008(75) 2
Lindblom et al., 2016(76) 2
Logemann et al., 1992(77) 3
Logemann et al., 2002(78) 5
Maruo et al., 2014(79) 2
Mercadante et al., 2015(80) 2
Moerman et al., 2003(81) 1
Montesi et al., 1990(82) 7
Muz et al., 1987(83) 2
Muz et al., 1991(84) 6
Nasef et al., 2016(85) 2
Nguyen et al., 2009(86) 2
Nikbakhsh et al., 2012(87) 2
Nilsson et al., na(88) 7
Nonoshita et al., 2010(89) 2
Oeken et al., 2001(90) 2
Ohba et al., 2016(91) 4
Ottosson et al., 2014(92) 2
Oursin et al., 1998(93) 2
Panchal et al., 1996(94) 6
Patterson et al., 2011(95) 5
Patterson et al., 2014(96) 2
Pauloski et al., 1993(97) 5
Pauloski et al., 1994(98) 5
60
Pauloski et al., 1995(99) 5
Pauloski et al., 1998(100) 5
Pauloski et al., 2000(101) 6
Pauloski et al., 2002(102) 5
Pauloski et al., 2006(103) 5
Pauloski et al., 2009(104) 5
Pauloski et al., 2015(105) 5
Paya et al., 2001(106) 1
Pearson et al., 2016(107) 5
Pedersen et al., 2016(108) 5
Peretti et al., 2006(109) 2
Peretti et al., 2013(110) 2
Piazza et al., 2016(111) 2
Pillon et al., 2004(112) 2
Portas et al., 2009(113) 7
Portas et al., 2011(114) 2
Posio et al., 2006(115) 7
Prgomet et al., 2002(116) 2
Queija et al., 2009(117) 2
Rahman et al., 2015(118) 2
Rhodus et al., 1995(119) 7
Roe et al., 2015(120) 2
Rutten et al., 2011(121) 2
Salama et al., 2008(122) 2
Samuels et al., 2016(123) 5
Santini et al., 2015(124) 4
Schache et al., 2009(125) 2
Silver et al., 2014(126) 6
Simonelli et al., 2010(127) 2
Smet et al., 2014(128) 2
So et al., 2014(129) 2
Soderstrom et al., 2017(130) 2
Sonoi et al., 2016(131) 2
Stachler et al., 1996(132) 6
Starmer et al., 2014(133) 2
Starmer et al., 2015(134) 2
Stecewicz et al., 2006(135) 7
Stephens et al., 2015(136) 2
Strasser et al., 2000(137) 1
Sugahara et al., 1996(138) 7
Szczesniak et al., 2014(139) 2
Szczesniak et al., 2015(140) 5
Takashima et al., 2010(141) 7
Teguh et al., 2008(142) 5
Tei et al., 2012(143) 4
Ursino, 2016(144) 3
Vainshtein et al., 2016(145) 2
Wall et al., 2016(146) 2
Wall et al., 2016(147) 2
Walther et al., 1990(148) 5
61
Walther et al., 1991(149) 5
Weber et al., 1991(150) 2
Wilson et al., 2011(151) 2
Yoo et al., 2012(152) 2
Yuceturk et al., 2005(153) 6
Zhang et al., 2016(154) 5
Zuydam et al., 2000(155) 2
(1) Patients without cancer or non-malignant tumors (n=4); (2) Studies that did not use VFSE, MBS or
FEES (image exam) as diagnose criteria for deglutition disorders before and after treatment for the
cancer (n=81); (3) Patients that did not underwent any type of treatment/ therapy for the cancer (n=3);
(4) Patients that are receiving treatment for the deglutition disorder/ or only patients with dysphagia
(n=4); (5) Studies that did not report values representative of the deglutition disorders (n=37); (6)
Reviews, letters, conference abstract, personal opinions, case reports, cross sectional, experimental
(n=12); (7) Full text not found (n=13); (8) Duplicated data Used sample and results from other study
(n=1).
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dissection]. Kokubyo Gakkai Zasshi. 2010;77(1):1-6.
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speech pathology/dietetic service model for providing supportive care intervention to head and neck
71
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147. Wall LR, Cartmill B, Ward EC, Hill AJ, Isenring E, Byrnes J, et al. “ScreenIT”: Computerized
screening of swallowing, nutrition and distress in head and neck cancer patients during (chemo)
radiotherapy. Oral oncology. 2016;54:47-53.
148. Walther EK, Rodel R, Deroover M. [Rehabilitation of deglutition in patients with pharyngeal
carcinoma]. Laryngorhinootologie. 1990;69(7):360-8.
149. Walther EK, Deroover M. [Video-fluoroscopy in a graduated diagnostic program in oral
cavity and pharyngeal carcinoma]. Laryngorhinootologie. 1991;70(9):491-6.
150. Weber RS, Ohlms L, Bowman J, Jacob R, Goepfert H. Functional results after total or near
total glossectomy with laryngeal preservation. Arch Otolaryngol Head Neck Surg. 1991;117(5):512-5.
151. Wilson JA, Carding PN, Patterson JM. Dysphagia after nonsurgical head and neck cancer
treatment: Patients' perspectives. Otolaryngology - Head and Neck Surgery. 2011;145(5):767-71.
152. Yoo DS, Kirkpatrick JP, Craciunescu O, Broadwater G, Peterson BL, Carroll MD, et al.
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advanced head and neck cancer. Clinical Cancer Research. 2012;18(5):1404-14.
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swallowing function after supracricoid laryngectomy. Eur Arch Otorhinolaryngol. 2005;262(3):198-
203.
154. Zhang T, Szczesniak M, Maclean J, Bertrand P, Wu PI, Omari T, et al. Biomechanics of
Pharyngeal Deglutitive Function following Total Laryngectomy. Otolaryngology-Head and Neck
Surgery. 2016;155(2):295-302.
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72
Appendix 3 - Risk of bias assessed in the included studies (n=16) by The Joanna Briggs Institute Critical Appraisal
Checklist for Studies Reporting Prevalence Data. Risk of bias was categorized as High when the study reaches up to
49% score “yes”, Moderate when the study reached 50% to 69% score “yes”, and Low when the study reached more
than 70% score “yes”.
Author,
Year Q1* Q2* Q3* Q4* Q5* Q6* Q7* Q8* Q9* Q10*
Score/Risk (the Not Applicable (NA) items
were excluded from the sum). Agarwal et
al., 2011(1) Y N Y Y Y Y Y Y N NA 77.7%/Low
Cartmill et
al., 2012(2) Y N N Y Y Y N Y N NA 55.5%/Moderate
Eisbruch et
al., 2002(3) Y N N Y Y Y Y Y N NA 66.6%/Moderate
Erkal et al.,
2014(4) Y N N N Y Y N Y N NA 44.4%/High
Graner et al.,
2003(5) Y N N Y Y Y N Y Y NA 66.6%/Moderate
Kotz et al.,
2004(6) Y N N Y Y Y Y Y Y NA 77.7%/Low
Ku et al.,
2007(7) Y N N Y Y Y Y Y N NA 66.6%/Moderate
Lazarus et al.,
2000(8) Y N N Y Y Y N Y Y NA 66.6%/Moderate
Logemann et
al., 2006(9) Y N Y Y Y Y Y Y N NA 77.7%/Low
Logemann et
al., 2008(10) Y N Y Y Y Y Y Y N NA 77.7%/Low
O’Connell et
al., 2008(11) Y N Y Y Y Y Y Y Y NA 88.8%/Low
Patterson et
al., 2014(12) Y N Y N Y Y Y Y Y NA 77.7%/Low
Rogus-Pulia
et al.,
2014(13) Y N N Y Y Y N Y Y NA 66.6%/Moderate
Serel et al.,
2013(14) Y N Y Y Y Y N Y Y NA 77.7%/Low
Son et al.,
2015(15) Y N Y Y Y Y N Y Y NA 77.7%/Low
Van der
Molen et al.,
2013(16) Y N Y Y Y Y Y Y N NA 77.7%/Low
Q1*: Was the sample representative of the target population?
Q2*: Were study participant recruited in an appropriate way?
Q3*: Was the sample size adequate?
Q4*: Were the study subjects and the setting described in detail?
Q5*: Was the data analysis conducted with sufficient coverage of the identified sample?
Q6*: Were objective, standard criteria used for the measurement of the condition?
Q7*: Was the condition measured reliably?
Q8*: Was there appropriate statistical analysis?
Q9*: Are all important confounding factors/ subgroups/ differences identified and accounted
for?
Q10*: Were subpopulations identified using objective criteria?
73
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2. Cartmill B, Cornwell P, Ward E, Davidson W, Porceddu S. A prospective investigation of
swallowing, nutrition, and patient-rated functional impact following altered fractionation radiotherapy
with concomitant boost for oropharyngeal cancer. Dysphagia. 2012;27(1):32-45.
3. Eisbruch A, Lyden T, Bradford CR, Dawson LA, Haxer MJ, Miller AE, et al. Objective
assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for
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structures. Radiotherapy and Oncology. 2013;106(3):364-9.
Appendix 4. Quality of the studies assessed with an adaptation for observational studies of
the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE)
system.
74
Quality assessment Summary of
findings
№ of
studies
Study
design
Ris
k of
bias
Inconsiste
ncy
Indirectn
ess Imprecision Impact Quality
Subgroups
Aspiration - Pretreatment
14 observatio
nal studies
serio
us a
not
serious
not serious not
serious
Proportion=11.31
%; CI 8.74-14.32;
p=0.0198; sample
size=517;
Inconsistency=49.
01%
⨁⨁⨁◯
MODERA
TE
Aspiration - 1 to 6 months posttreatment
13 observatio
nal studies
serio
us a
serious b
not serious not
serious
Proportion=27.3
%; CI 19.03-
36.07; p<0.0001;
sample size=478;
Inconsistency=76.
22%
⨁⨁◯◯
LOW
Aspiration - over 6 months posttreatment
7 observatio
nal studies
serio
us a
not
serious
not serious not
serious
Proportion=17.99
%; CI 12.37-
24.83; p=0.1316;
sample size=153;
Inconsistency=39.
02%
⨁⨁⨁◯
MODERA
TE
Penetration above the vocal cords - Pretreatment
6 observatio
nal studies
serio
us a
not
serious
not serious not
serious
Proportion=14.73
%; CI 8.90-22.39;
p=0.2839; sample
size= 113;
Inconsistency=19.
82%
⨁⨁⨁◯
MODERA
TE
Penetration above the vocal cords - 1 to 6 months posttreatment
6 observatio
nal studies
serio
us a
serious b
not serious not
serious
Proportion=37.19
%; CI 23.22-
52.36; p=0.0142;
sample size=113;
Inconsistency=64.
88%
⨁⨁◯◯
LOW
Penetration above the vocal cords - over 6 months posttreatment
75
Quality assessment Summary of
findings
№ of
studies
Study
design
Ris
k of
bias
Inconsiste
ncy
Indirectn
ess Imprecision Impact Quality
Subgroups
4 observatio
nal studies
serio
us a
serious b
not serious not
serious
Proportion=33.22
%; CI 11.58-
59.54; p=0.0004;
sample size=80;
inconsistency=83.
70%
⨁⨁◯◯
LOW
Reduced laryngeal elevation - Pretreatment
4 observatio
nal studies
not
serio
us
serious b
not serious not
serious
Proportion=14.17
%; CI 1.51-36.50;
p<0.0001; sample
size=204;
Inconsistency=89.
85%
⨁⨁⨁◯
MODERA
TE
Reduced laryngeal elevation - 1 to 6 months posttreatment
4 observatio
nal studies
not
serio
us
serious b
not serious not
serious
Proportion=50.38
%; CI 15.36-
85.18; p<0.0001;
sample size=204;
Inconsistency=95.
43%
⨁⨁⨁◯
MODERA
TE
CI: Confidence interval
Explanations
a. One of the study included in this analysis was classified as high risk of bias.
b. Inconsistency in the meta-analysis over 50%
GRADE Working Group grades of evidence:
High quality: We are very confident that the true effect lies close to that of the estimate of the
effect.
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely
to be close to the estimate of the effect, but there is a possibility that it is substantially
different.
Low quality: Our confidence in the effect estimate is limited: The true effect may be
substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: The true effect is
likely to be substantially different from the estimate of effect.
76
6. CONSIDERAÇÕES GERAIS
Os objetivos desse estudo consistiam em coletar, analisar e comparar os
resultados encontrados na literatura sobre a frequência de desordens de
deglutição e alterações associadas, em pacientes com CCP pré e pós-tratamento
oncológico. Observou-se que há maior frequência de complicações no pós-
tratamento imediato (1 a 6 meses), quando comparado ao pré-tratamento e aos
períodos mais longos após finalização das terapias (>6 meses). Esse resultado
encontrado é semelhante a outros estudos. No período imediato pós-tratamento
de CCP com a modalidade IMRT, disfagia foi referida por 75% da amostra,
reduzindo para 14% após 6 meses da finalização do tratamento33.
Dos estudos incluídos na RS, nenhum deles apresentou acompanhamento do
paciente por período acima de um ano. Dados coletados por períodos mais
longos podem trazer informações relevantes quanto à qualidade de vida e
prognóstico desses pacientes. Numa amostra acompanhada por uma média de
21 meses pós-tratamento, foram observados que 35% dos participantes
possuíam modificação na consistência da dieta (pastosa) e 20% faziam uso de
alimentação por via alternativa34. Similarmente, num acompanhamento médio de
44 meses pós-tratamento em pacientes com CCP, 57% apresentaram alterações
na deglutição avaliada por videofluoroscopia35. A presença de disfagia a longo
tempo após tratamento oncológico também pode ser um dos indicadores para
recorrência da doença36.
No que concerne às limitações desse estudo, foi observado uma
heterogeneidade quanto às formas de avaliação e classificação das desordens e
alterações relacionadas à deglutição. A avaliação, identificação e tratamento das
sequelas orais/orofaríngeas geradas pelo CCP apresentam desafios e falta de
métodos sistemáticos adotados mundialmente. Para a avaliação de deglutição,
alguns exemplos são os exames objetivos: videofluoroscopia e videoendoscopia
da deglutição37. Além deles a coleta do histórico e sintomatologia do paciente
também é de suma importância, assim como avaliação clínica.
A variação nos períodos de acompanhamento dos pacientes nos estudos
incluídos, também foi uma das limitações encontradas. Esse fator influenciou a
análise realizada, pois, o número de estudos incluídos na análise na fase pré-
tratamento (14 estudos38-50 na análise de aspiração) foi maior que a quantidade
77
incluída nas análises das fases pós-tratamento oncológico (738-41,43,46,50 estudos
na análise de aspiração até 12 meses). Outra variação que influencia na
consideração dos dados analisados são as diferentes modalidades de tratamento
oncológico empregadas nos estudos. Quase todos os estudos incluídos38-49,51,52
apresentaram amostras que foram tratadas por radioterapia e quimioterapia
associadas ou não à cirurgia. Adicionalmente, apenas um estudo50 apresentou
dados de pacientes tratados com a modalidade IMRT associada a quimioterapia.
O tratamento de radioterapia com uso de IMRT, associado ao não a
imagem guiada, para pacientes com CCP vem se propagando. A IMRT
associada à técnica para poupar glândulas salivares pode auxiliar na diminuição
de sequelas como a xerostomia 53,54. A longo tempo (1 a 2 anos), apenas 18% e
21% dos pacientes com CCP tratados com esse tipo de radioterapia,
apresentavam xerostomia e disfagia, respectivamente55.
78
7. CONCLUSÃO
A partir dos objetivos estabelecidos e resultados encontrados, pode-se
concluir que:
• Na literatura há poucos estudos que analisem desordens de deglutição
com exames objetivos comparando dados do pré e pós-tratamento
oncológico do CCP;
• A frequência de desordens da deglutição é alta na população com
CCP;
• Observou-se uma frequência mais alta de alterações no pós-tratamento
oncológico imediato quando comparado ao pré-tratamento e períodos
mais longos (até 12 meses);
• Há ainda lacuna na literatura para estudos longitudinais, com
acompanhamento do paciente de CCP num período superior a 12
meses. Também é necessário a realização de avaliação da deglutição
com exames objetivos e estabelecendo classificação padronizada para
as alterações encontradas.
79
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